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The influence of subanaesthetic ketamine on regional cerebral blood flow in healthy dogs measured with 99mTc-HMPAO SPECT

Lise Vlerick (UGent) , Kathelijne Peremans (UGent) , Robrecht Dockx (UGent) , Kurt Audenaert (UGent) , Chris Baeken (UGent) , Bart De Spiegeleer (UGent) , Jimmy Saunders (UGent) and Ingeborgh Polis (UGent)
(2018) PLOS ONE. 13(12).
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Abstract
Subanaesthetic ketamine has recently been proven to be a highly effective and fast acting alternative treatment for several psychiatric disorders. The mechanisms responsible for ketamine's antidepressant effects remain unclear, but a possible explanation could be that ketamine interacts with regional cerebral blood flow (rCBF). Therefore, the effects of two subanaesthetic ketamine doses on rCBF were evaluated. Twelve dogs were randomly assigned to one of the three treatment conditions (condition saline, condition 0.5 mg/kg ketamine or condition 2 mg/kg ketamine) and received in total five saline or ketamine infusions, with one week interval. Single Photon Emission Computed Tomography (SPECT) scans with the radiotracer Tc-99m-hexamethylpropylene amine oxime were performed before the start of the infusions (baseline) and 24 hours after the first (single) and last (multiple) infusion. After a wash out period of 3 months, the animals were again assigned to one of the three treatment conditions described above and the infusion/scan protocol was repeated. During the infusions, cardiovascular parameters were evaluated every ten minutes. A one-way repeated measure ANOVA was set up to assess perfusion index for each ketamine dose for the left frontal cortex (alpha = 0.05). The remaining 11 brain regions were post hoc assessed. Perfusion index was significantly increased in the left frontal cortex and in the thalamus 24 hours after single and multiple ketamine infusions compared to baseline in the 2 mg/kg condition. No clinically relevant cardiovascular effects were observed during the ketamine infusions. This study shows that subanaesthetic ketamine can increase neuronal perfusion and therefore alter neuronal function in brain regions involved in depression and anxiety disorders. These perfusion increases may possibly contribute to ketamine's beneficial effects in these psychiatric disorders.
Keywords
ELECTROCONVULSIVE-THERAPY, UNIPOLAR DEPRESSION, ANXIETY DISORDERS, BINDING INDEX, ANTIDEPRESSANT, RECEPTOR, PERFUSION, BEHAVIOR, PET, MEDETOMIDINE

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MLA
Vlerick, Lise, Kathelijne Peremans, Robrecht Dockx, et al. “The Influence of Subanaesthetic Ketamine on Regional Cerebral Blood Flow in Healthy Dogs Measured with 99mTc-HMPAO SPECT.” PLOS ONE 13.12 (2018): n. pag. Print.
APA
Vlerick, Lise, Peremans, K., Dockx, R., Audenaert, K., Baeken, C., De Spiegeleer, B., Saunders, J., et al. (2018). The influence of subanaesthetic ketamine on regional cerebral blood flow in healthy dogs measured with 99mTc-HMPAO SPECT. PLOS ONE, 13(12).
Chicago author-date
Vlerick, Lise, Kathelijne Peremans, Robrecht Dockx, Kurt Audenaert, Chris Baeken, Bart De Spiegeleer, Jimmy Saunders, and Ingeborgh Polis. 2018. “The Influence of Subanaesthetic Ketamine on Regional Cerebral Blood Flow in Healthy Dogs Measured with 99mTc-HMPAO SPECT.” Plos One 13 (12).
Chicago author-date (all authors)
Vlerick, Lise, Kathelijne Peremans, Robrecht Dockx, Kurt Audenaert, Chris Baeken, Bart De Spiegeleer, Jimmy Saunders, and Ingeborgh Polis. 2018. “The Influence of Subanaesthetic Ketamine on Regional Cerebral Blood Flow in Healthy Dogs Measured with 99mTc-HMPAO SPECT.” Plos One 13 (12).
Vancouver
1.
Vlerick L, Peremans K, Dockx R, Audenaert K, Baeken C, De Spiegeleer B, et al. The influence of subanaesthetic ketamine on regional cerebral blood flow in healthy dogs measured with 99mTc-HMPAO SPECT. PLOS ONE. 2018;13(12).
IEEE
[1]
L. Vlerick et al., “The influence of subanaesthetic ketamine on regional cerebral blood flow in healthy dogs measured with 99mTc-HMPAO SPECT,” PLOS ONE, vol. 13, no. 12, 2018.
@article{8587839,
  abstract     = {Subanaesthetic ketamine has recently been proven to be a highly effective and fast acting alternative treatment for several psychiatric disorders. The mechanisms responsible for ketamine's antidepressant effects remain unclear, but a possible explanation could be that ketamine interacts with regional cerebral blood flow (rCBF). Therefore, the effects of two subanaesthetic ketamine doses on rCBF were evaluated. Twelve dogs were randomly assigned to one of the three treatment conditions (condition saline, condition 0.5 mg/kg ketamine or condition 2 mg/kg ketamine) and received in total five saline or ketamine infusions, with one week interval. Single Photon Emission Computed Tomography (SPECT) scans with the radiotracer Tc-99m-hexamethylpropylene amine oxime were performed before the start of the infusions (baseline) and 24 hours after the first (single) and last (multiple) infusion. After a wash out period of 3 months, the animals were again assigned to one of the three treatment conditions described above and the infusion/scan protocol was repeated. During the infusions, cardiovascular parameters were evaluated every ten minutes. A one-way repeated measure ANOVA was set up to assess perfusion index for each ketamine dose for the left frontal cortex (alpha = 0.05). The remaining 11 brain regions were post hoc assessed. Perfusion index was significantly increased in the left frontal cortex and in the thalamus 24 hours after single and multiple ketamine infusions compared to baseline in the 2 mg/kg condition. No clinically relevant cardiovascular effects were observed during the ketamine infusions. This study shows that subanaesthetic ketamine can increase neuronal perfusion and therefore alter neuronal function in brain regions involved in depression and anxiety disorders. These perfusion increases may possibly contribute to ketamine's beneficial effects in these psychiatric disorders.},
  articleno    = {e0209316},
  author       = {Vlerick, Lise and Peremans, Kathelijne and Dockx, Robrecht and Audenaert, Kurt and Baeken, Chris and De Spiegeleer, Bart and Saunders, Jimmy and Polis, Ingeborgh},
  issn         = {1932-6203},
  journal      = {PLOS ONE},
  keywords     = {ELECTROCONVULSIVE-THERAPY,UNIPOLAR DEPRESSION,ANXIETY DISORDERS,BINDING INDEX,ANTIDEPRESSANT,RECEPTOR,PERFUSION,BEHAVIOR,PET,MEDETOMIDINE},
  language     = {eng},
  number       = {12},
  pages        = {15},
  title        = {The influence of subanaesthetic ketamine on regional cerebral blood flow in healthy dogs measured with 99mTc-HMPAO SPECT},
  url          = {http://dx.doi.org/10.1371/journal.pone.0209316},
  volume       = {13},
  year         = {2018},
}

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